Bioenergetic markers in cerebrospinal fluid in first-episode psychosis: Are they predictors of early antipsychotic response and 1-year outcomes?

Psychotic disorders involve complex pathophysiological mechanisms, and identification of biomarkers for treatment response remains a major challenge. We aimed to study whether routine cerebrospinal fluid (CSF) parameters measured at baseline predict poor early response at 2 weeks with optimal antipsychotic treatment doses in patients with first-episode psychosis (FEP). We also explored whether these parameters could predict changes in social functioning and psychopathology over a 1-year follow-up. Ninety-eight inpatients with FEP who had received less than 6 weeks of antipsychotic treatment were included in the study. A lumbar puncture was performed at the index admission to measure CSF parameters (glucose, total protein, and lactate dehydrogenase [LDH]). The Positive and Negative Syndrome Scale (PANSS) was administered. A poor early treatment response at week 2 was defined as a < 20 % reduction in the PANSS positive subscore of a consensus factor. Social functioning was assessed using the Personal and Social Performance Scale (PSP) at baseline and 2, 4, 6, 9, and 12 months. Statistical analyses explored the role of CSF biomarkers in early treatment response using logistic regression and long-term social functioning and psychopathology using mixed linear regression analyses. Eighteen patients with FEP (18.4 %) were nonresponders at week 2. The CSF LDH concentration was a predictor of early treatment nonresponse. Higher CSF LDH concentrations were associated with a reduced improvement in social functioning at month 2, and higher CSF glucose concentrations were associated with lower reductions in the PANSS total scores at all visits. These findings suggest that specific bioenergetic parameters in the CSF, such as LDH and glucose, may serve as prognostic biomarkers for early treatment response and 1-year social and psychopathological outcomes in patients with FEP.